PROJECT SUMMARY/ABSTRACT: TARGETED ANALYSIS RESOURCE The Minnesota HHEAR Targeted Analysis Resource will combine the vast analytical chemistry expertise of investigators at the University of Minnesota and the Public Health Laboratory, Minnesota Department of Health. This Targeted Analysis Resource will serve the research community by providing state-of-the art quantitative analyses of biomarkers directly indicative of environmental chemical exposures including parent compounds, metabolites, and DNA or protein adducts. This Targeted Analysis Resource builds on the established methods and expertise that have been applied successfully in the Minnesota Targeted Analysis Resource of the CHEAR program. The Targeted Analysis Resource will provide timely and reliable quantitative data in three major areas of environmental and lifestyle exposures highly relevant to human health: 1. Exposure to tobacco-specific compounds; 2. Exposure to environmental, lifestyle, and nutritional toxicants and cacinogens; 3. Variations in levels of endogenous and dietary compounds. The tobacco-specific compounds are critical for establishing exposure to tobacco products or e-cigarettes. They include the full suite of urinary nicotine metabolites (nicotine, cotinine, 3?-hydroxycotinine and their glucuronides, and nicotine-N-oxide); cotinine and 3?-hydroxycotinine in serum, dried blood spots, and toenails; and the tobacco-specific carcinogen metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides in urine, blood, and toenails. The environmental, lifestyle, and nutritional toxicants and carcinogens and metabolites include mercapturic acid (MA) metabolites of volatile toxicants such as acrylonitrile (CEMA), benzene (SPMA), acrolein (3-HPMA), crotonaldehyde (HMPMA), and ethylene oxide (HEMA); urinary metabolites of furan; urinary metabolites of polycyclic aromatic hydrocarbons (PAH) such as 1-hydroxypyrene (1-HOP) and phenanthrene tetraol (PheT); urinary metals; per- and polyfluoroalkyl substances; opioids, cannabinoids, and designer drugs; leukocyte DNA adducts of formaldehyde, acetaldehyde, and acrolein; and DNA adducts of heterocyclic aromatic amines in formalin fixed paraffin embedded tissues. The endogenous and dietary compounds include the carcinogenic urinary heterocyclic aromatic amines 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6- pheynylimidazo[4,5-b]pyridine (PhIP) and their metabolites; PhIP in hair; tissue 8-hydroxydeoxyguanosine; plasma carotenes, lycopenes, tocopherols, ascorbic acid, vitamin D derivatives, isoprostanes, and urinary polyphenols.